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Lipoxygenase

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https://www.readbyqxmd.com/read/28723225/preferential-generation-of-15-hete-pe-induced-by-il-13-regulates-goblet-cell-differentiation-in-human-airway-epithelial-cells
#1
Jinming Zhao, Yoshinori Minami, Emily Etling, John M Coleman, Sarah N Lauder, Victoria Tyrrell, Maceler Aldrovandi, Valerie O'Donnell, Hans-Erik Claesson, Valerian Kagan, Sally Wenzel
RATIONALE: Type-2-associated goblet cell hyperplasia and mucus hypersecretion are well known features of asthma. 15-Lipoxygenase (15LO1) is induced by the Type-2 cytokines/IL-13 in human airway epithelial cells (HAEC) in vitro and is increased in fresh asthmatic HAECs ex vivo. 15LO1 generates a variety of products, including 15-hydroxyeicosatetraenoic acid (15-HETE), 15-HETE-phosphatidyethanoloamine (PE) (15-HETE-PE) and 13-hydroxyoctadecadienoic acid (13-HODE). The current study investigated the 15LO1 metabolite profile at baseline and after IL-13 treatment, and the influence on goblet cell differentiation in HAECs...
July 19, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28721338/is-aortic-aneurysm-preventable
#2
Undurti N Das
Abdominal aortic aneurysm (AAA) is a chronic inflammatory condition, triggered by the local accumulation of macrophages, oxidative stress and damage to the aortic wall. Pro-inflammatory eicosanoids seem to play a significant role in AAA. The pro-inflammatory events seen in AAA could be due to a deficiency of anti-inflammatory eicosanoids such as lipoxin A4 (LXA4), resolvins, protectins and maresins as a result of reduced tissue concentrations of their precursors: arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA)...
June 2017: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28720379/inhibition-of-12-15-lox-ameliorates-cognitive-and-cholinergic-dysfunction-in-mouse-model-of-hypobaric-hypoxia-via-attenuation-of-oxidative-nitrosative-stress
#3
Richa Choudhary, Udayabanu Malairaman, Anju Katyal
12/15 Lipoxygenase has recently been described as potent propagator of oxidative stress and is closely associated with cognitive decline in neurodegenerative diseases. The mechanism/s behind 12/15 LOX involvement in cognitive deficits remain obscure. The current study has been designed to investigate the underlying role of 12/15LOX and effect of 12/15 LOX inhibition on hypobaric hypoxia induced memory impairment and cholinergic deficits. Male Balb/c mice subjected to simulated hypobaric hypoxia/reoxygenation condition for 3 days showed marked working memory impairment concomitant with hippocampal neuronal damage and malondialdehyde production which were significantly attenuated by baicalein, a specific inhibitor of 12/15LOX...
July 15, 2017: Neuroscience
https://www.readbyqxmd.com/read/28715485/characterization-of-the-maize-lipoxygenase-gene-family-in-relation-to-aflatoxin-accumulation-resistance
#4
Oluwaseun F Ogunola, Leigh K Hawkins, Erik Mylroie, Michael V Kolomiets, Eli Borrego, Juliet D Tang, W Paul Williams, Marilyn L Warburton
Maize (Zea mays L.) is a globally important staple food crop prone to contamination by aflatoxin, a carcinogenic secondary metabolite produced by the fungus Aspergillus flavus. An efficient approach to reduce accumulation of aflatoxin is the development of germplasm resistant to colonization and toxin production by A. flavus. Lipoxygenases (LOXs) are a group of non-heme iron containing dioxygenase enzymes that catalyze oxygenation of polyunsaturated fatty acids (PUFAs). LOX derived oxylipins play critical roles in plant defense against pathogens including A...
2017: PloS One
https://www.readbyqxmd.com/read/28713783/streptococcus-pyogenes-phospholipase-a2-induces-the-expression-of-adhesion-molecules-on-human-umbilical-vein-endothelial-cells-and-aorta-of-mice
#5
Masataka Oda, Hisanori Domon, Mie Kurosawa, Toshihito Isono, Tomoki Maekawa, Masaya Yamaguchi, Shigetada Kawabata, Yutaka Terao
The Streptococcus pyogenes phospholipase A2 (SlaA) gene is highly conserved in the M3 serotype of group A S. pyogenes, which often involves hypervirulent clones. However, the role of SlaA in S. pyogenes pathogenesis is unclear. Herein, we report that SlaA induces the expression of intercellular adhesion molecule 1 (ICAM1) and vascular cell adhesion molecule 1 (VCAM1) via the arachidonic acid signaling cascade. Notably, recombinant SlaA induced ICAM1 and VCAM1 expression in human umbilical vein endothelial cells (HUVECs), resulting in enhanced adhesion of human monocytic leukemia (THP-1) cells...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28711978/the-activity-of-the-antioxidant-defense-system-of-the-weed-species-senna-obtusifolia-l-and-its-resistance-to-allelochemical-stress
#6
Érica Marusa Pergo Coelho, Mauro Cezar Barbosa, Márcio Shigueaki Mito, Gislaine Cristiane Mantovanelli, Rubem Silvério Oliveira, Emy Luiza Ishii-Iwamoto
Senna obtusifolia L., a common weed in the tropical and subtropical regions of the world, is able to germinate under adverse environmental conditions, suggesting that this species has efficient stress-adaptation strategies. The aims of the present work were to examine the energy metabolism and the antioxidant defense system of the Senna obtusifolia L. during seed germination and initial growth, and the responses to allelochemical-induced stress. Respiratory activity, the activities of alcohol dehydrogenase (ADH), superoxide dismutase (SOD), catalase (CAT),guaicol peroxidase (POD), ascorbate peroxidase (APX), glutathione reductase (GR), lipoxygenase (LOX) and the content of malondialdehyde (MDA) and glutathione (GSSG and GSH) were measured...
July 15, 2017: Journal of Chemical Ecology
https://www.readbyqxmd.com/read/28710425/naja-sputatrix-venom-preconditioning-attenuates-neuroinflammation-in-a-rat-model-of-surgical-brain-injury-via-pla2-5-lox-ltb4-cascade-activation
#7
Yuechun Wang, Prativa Sherchan, Lei Huang, Onat Akyol, Devin W McBride, John H Zhang
Inflammatory preconditioning is a mechanism in which exposure to small doses of inflammatory stimuli prepares the body against future massive insult by activating endogenous protective responses. Phospholipase A2/5-lipoxygenase/leukotriene-B4 (PLA2/5-LOX/LTB4) axis is an important inflammatory signaling pathway. Naja sputatrix (Malayan spitting cobra) venom contains 15% secretory PLA2 of its dry weight. We investigated if Naja sputatrix venom preconditioning (VPC) reduces surgical brain injury (SBI)-induced neuroinflammation via activating PLA2/5-LOX/LTB4 cascade using a partial frontal lobe resection SBI rat model...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28704416/genetic-variation-in-the-eicosanoid-pathway-is-associated-with-non-small-cell-lung-cancer-nsclc-survival
#8
Lindsay N Sausville, Carissa C Jones, Melinda C Aldrich, William J Blot, Ambra Pozzi, Scott M Williams
Globally, lung cancer results in more deaths worldwide than any other cancer, indicating a need for better treatments. Members of the eicosanoid metabolism pathway represent promising therapeutic targets, as several enzymes involved in the generation of these lipids are dysregulated in many cancers and their inhibition reduces lung cancer growth in mouse models. However, genetic variation of enzymes involved in eicosanoid metabolism has not been adequately examined for association with lung cancer. The goal of this study was to determine whether germline genetic variation altering eicosanoid producing enzyme function and/or expression are associated with differences in lung cancer survival...
2017: PloS One
https://www.readbyqxmd.com/read/28701359/oxldl-induced-endothelial-proliferation-via-rho-rock-akt-p27-kip1-signaling-prevention-by-cholesterol-loading
#9
Chongxu Zhang, Crystal Adamos, Myung-Jin Oh, Jugajyoti Baruah, Manuela A A Ayee, Dolly Mehta, Kishore K Wary, Irena Levitan
Oxidized modifications of LDL (oxLDL) are known to play a major role in endothelial dysfunction and the development of atherosclerosis. In this study, we provide comparative analysis of the effects of two major types of oxLDL, copper oxidized LDL (Cu(2+)-oxLDL) and Lipoxygenase oxidized LDL (LPO-oxLDL) on proliferation of Human Aortic Endothelial Cells (HAECs). We show that Cu(2+)-oxLDL enhances HAECs proliferation in a dose and oxidation-dependent manner. Similarly, LPO-oxLDL also has a positive effect on HAECs proliferation...
July 12, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28701173/15-oxoeicosatetraenoic-acid-mediates-monocyte-adhesion-to-endothelial-cell
#10
Guohua Ma, Bing Pan, Sufen Ren, Caixia Guo, Yansong Guo, Lixin Wei, Lemin Zheng, Buxing Chen
BACKGROUND: A great number of studies reported that 12/15-lipoxygenase (12/15-LO) played an important role in atherosclerosis. And its arachidonic acid(AA) metabolite, 15(S)-hydroperoxy-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15(S)-HETE), is demonstrated to mediate endothelial dysfunction. 15-oxo-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-oxo-ETE) was formed from 15-hydroxyprostaglandin dehydrogenase (PGDH)-mediated oxidation of 15(S)-HETE. However, relatively little is known about the biological effects of 15-oxo-ETE in cardiovascular disease...
July 12, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28699354/drug-mediated-intracellular-donation-of-nitric-oxide-potently-inhibits-5-lipoxygenase-a-possible-key-to-future-anti-leukotriene-therapy
#11
Jessica Roos, Marcus Peters, Isabelle V Maucher, Benjamin Kühn, Jasmin Fettel, Nadine Hellmuth, Camilla Brat, Benita Sommer, Anja Urbschat, Matthias Piesche, Anja Vogel, Ewgenij Proschak, René Blöcher, Estel la Buscato, Ann-Kathrin Häfner, Carmela Matrone, Oliver Werz, Juliana Heidler, Ilka Wittig, Carlo Angioni, Gerd Geisslinger, Michael J Parnham, Kai Zacharowski, Dieter Steinhilber, Thorsten Jürgen Maier
AIMS: 5-lipoxygenase (5-LO) is the key enzyme of leukotriene biosynthesis and is critically involved in a number of inflammatory diseases such as arthritis, gout, bronchial asthma, atherosclerosis and cancer. Because 5-LO contains critical nucleophilic amino acids, which are sensitive to electrophilic modifications, we determined the consequences of a drug-mediated intracellular release of nitric oxide (NO) on 5-LO product formation by human granulocytes and on 5-LO-dependent pulmonary inflammation in vivo...
July 12, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28694473/5-lo-inhibition-ameliorates-palmitic-acid-induced-er-stress-oxidative-stress-and-insulin-resistance-via-ampk-activation-in-murine-myotubes
#12
Hyun Jeong Kwak, Hye-Eun Choi, Hyae Gyeong Cheon
Leukotriene B4 (LTB4) production via the 5-lipoxygenase (5-LO) pathway contributes to the development of insulin resistance in adipose and hepatic tissues, but the role of LTB4 in skeletal muscle is relatively unknown. Here, the authors investigated the role of LTB4 in C2C12 myotubes in palmitic acid (PA)-induced ER stress, inflammation and insulin resistance. PA (750 μM) evoked lipotoxicity (ER stress, oxidative stress, inflammation and insulin resistance) in association with LTB4 production. 5-LO inhibition reduced all the lipotoxic effects induced by PA...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694081/accelerated-development-of-aging-associated-and-instability-induced-osteoarthritis-in-12-15-lipoxygenase-deficient-mice
#13
Lauris Habouri, Fatima Ezzahra El Mansouri, Yassine Ouhaddi, Bertrand Lussier, Jean-Pierre Pelletier, Johanne Martel-Pelletier, Mohamed Benderdour, Hassan Fahmi
OBJECTIVE: 12/15-Lipoxygenase (12/15-LOX) catalyzes the generation of various anti-inflammatory lipid mediators, and has been implicated in several inflammatory and degenerative diseases. However, there is currently no evidence that 12/15-LOX has a role in osteoarthritis (OA). The aim of this study was to investigate the role of 12/15-LOX in the pathogenesis of OA. METHODS: The development of aging-associated and destabilization of the medial meniscus (DMM)-induced OA were compared in 12/15-LOX-deficient (12/15-LOX-/-) and wild-type (WT) mice...
July 7, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28691068/hydrogen-deuterium-exchange-of-lipoxygenase-uncovers-a-relationship-between-distal-solvent-exposed-protein-motions-and-the-thermal-activation-barrier-for-catalytic-proton-coupled-electron-tunneling
#14
Adam R Offenbacher, Shenshen Hu, Erin M Poss, Cody A M Carr, Alexander D Scouras, Daniil M Prigozhin, Anthony T Iavarone, Ali Palla, Tom Alber, James S Fraser, Judith P Klinman
Defining specific pathways for efficient heat transfer from protein-solvent interfaces to their active sites represents one of the compelling and timely challenges in our quest for a physical description of the origins of enzyme catalysis. Enzymatic hydrogen tunneling reactions constitute excellent systems in which to validate experimental approaches to this important question, given the inherent temperature independence of quantum mechanical wave function overlap. Herein, we present the application of hydrogen-deuterium exchange coupled to mass spectrometry toward the spatial resolution of protein motions that can be related to an enzyme's catalytic parameters...
June 28, 2017: ACS Central Science
https://www.readbyqxmd.com/read/28690055/antitumor-effect-of-ferula-assa-foetida-oleo-gum-resin-against-breast-cancer-induced-by-4t1-cells-in-balb-c-mice
#15
Seyyed Majid Bagheri, Amir Abdian-Asl, Mahin Taheri Moghadam, Maryam Yadegari, Aghdas Mirjalili, Fatemeh Zare-Mohazabieh, Haniyeh Momeni
BACKGROUND: Ferula assa foetida commonly consumed as a healthy beverage has been demonstrated to have various biological activities, including antioxidation, anti-obesity and anti-cancer. OBJECTIVE: Our study aims to investigate the antitumor effect of asafoetida in vivo using mouse mammary carcinoma 4T1 cells. MATERIALS AND METHODS: In the study, female BALB/c mice were divided into two groups (n = 6), which were control (untreated) and other group of mice with breast cancer treated with 100 mg/kg of asafoetida, respectively, by oral gavage...
July 6, 2017: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/28684707/substituted-caffeic-and-ferulic-acid-phenethyl-esters-synthesis-leukotrienes-biosynthesis-inhibition-and-cytotoxic-activity
#16
Pier Morin, Patrick-Denis St-Coeur, Jérémie A Doiron, Marc Cormier, Julie J Poitras, Marc E Surette, Mohamed Touaibia
Glioblastoma multiforme (GBM) is an aggressive brain tumor that correlates with short patient survival and for which therapeutic options are limited. Polyphenolic compounds, including caffeic acid phenethyl ester (CAPE, 1a), have been investigated for their anticancer properties in several types of cancer. To further explore these properties in brain cancer cells, a series of caffeic and ferulic acid esters bearing additional oxygens moieties (OH or OCH₃) were designed and synthesized. (CAPE, 1a), but not ferulic acid phenethyl ester (FAPE, 1b), displayed substantial cytotoxicity against two glioma cell lines...
July 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28680195/new-hydroxycinnamic-acid-esters-as-novel-5-lipoxygenase-inhibitors-that-affect-leukotriene-biosynthesis
#17
Luc H Boudreau, Grégoire Lassalle-Claux, Marc Cormier, Sébastien Blanchard, Marco S Doucet, Marc E Surette, Mohamed Touaibia
Leukotrienes are inflammatory mediators that actively participate in the inflammatory response and host defense against pathogens. However, leukotrienes also participate in chronic inflammatory diseases. 5-lipoxygenase is a key enzyme in the biosynthesis of leukotrienes and is thus a validated therapeutic target. As of today, zileuton remains the only clinically approved 5-lipoxygenase inhibitor; however, its use has been limited due to severe side effects in some patients. Hence, the search for a better 5-lipoxygenase inhibitor continues...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28678785/dependency-of-a-therapy-resistant-state-of-cancer-cells-on-a-lipid-peroxidase-pathway
#18
Vasanthi S Viswanathan, Matthew J Ryan, Harshil D Dhruv, Shubhroz Gill, Ossia M Eichhoff, Brinton Seashore-Ludlow, Samuel D Kaffenberger, John K Eaton, Kenichi Shimada, Andrew J Aguirre, Srinivas R Viswanathan, Shrikanta Chattopadhyay, Pablo Tamayo, Wan Seok Yang, Matthew G Rees, Sixun Chen, Zarko V Boskovic, Sarah Javaid, Cherrie Huang, Xiaoyun Wu, Yuen-Yi Tseng, Elisabeth M Roider, Dong Gao, James M Cleary, Brian M Wolpin, Jill P Mesirov, Daniel A Haber, Jeffrey A Engelman, Jesse S Boehm, Joanne D Kotz, Cindy S Hon, Yu Chen, William C Hahn, Mitchell P Levesque, John G Doench, Michael E Berens, Alykhan F Shamji, Paul A Clemons, Brent R Stockwell, Stuart L Schreiber
Plasticity of the cell state has been proposed to drive resistance to multiple classes of cancer therapies, thereby limiting their effectiveness. A high-mesenchymal cell state observed in human tumours and cancer cell lines has been associated with resistance to multiple treatment modalities across diverse cancer lineages, but the mechanistic underpinning for this state has remained incompletely understood. Here we molecularly characterize this therapy-resistant high-mesenchymal cell state in human cancer cell lines and organoids and show that it depends on a druggable lipid-peroxidase pathway that protects against ferroptosis, a non-apoptotic form of cell death induced by the build-up of toxic lipid peroxides...
July 5, 2017: Nature
https://www.readbyqxmd.com/read/28676689/eicosapentaenoic-acid-and-5-hepe-enhance-macrophage-mediated-treg-induction-in-mice
#19
Toshiharu Onodera, Atsunori Fukuhara, Jihoon Shin, Tomonori Hayakawa, Michio Otsuki, Iichiro Shimomura
Eicosapentaenoic acid (EPA) is an omega-3 fatty acid with immunomodulatory and anti-inflammatory effects. Beyond its direct effects, the metabolic products of EPA also regulate various immune responses. Animal experiments demonstrated that EPA reduces adipose inflammation in high fat diet-induced obese mouse. However, the effects of EPA on infiltrated immune cell populations in adipose tissue and underlying mechanisms remain to be elucidated. We performed flow cytometry of stromal vascular fraction of epididymal adipose tissues from C57BL/6J and ob/ob mice fed normal chow mixed with or without 5% EPA...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28675447/cosmetic-potentials-of-prunus-domestica-l
#20
Emilie Stierlin, Stéphane Azoulay, Lionel Massi, Xavier Fernandez, Thomas Michel
BACKGROUND: The current study presents new insight in the phytochemical content and biological activities of five Prunus domestica L. varieties ('Quetsche blanche de Létricourt', 'Mirabelle de Nancy', 'Perdrigon violet', 'Mirabelle de Provence' and 'Reine-claude dorée'). RESULTS: The plum leaves were found to possess promising anti-ageing activities by their capacity to inhibit DPPH, elastase, hyaluronidase and lipoxygenase. After solid phase extraction (SPE), chlorogenic acid, rutin, quercetin and their derivatives were putatively identified by HPLC-ESI-MS/MS...
July 4, 2017: Journal of the Science of Food and Agriculture
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